Nitrosopersulfide (SSNO ­ ) is a potential protein Cys polysulfidating agent with sustained and long-range effects

The biological actions of NO and H 2 S are intimately intertwined. Chemical interactions of these molecules form a network of cascading chemicals. SSNO ­ is a major product of these interactions. It is relatively stable under physiological conditions and not reducible by thiols. Upon slow decomposition of SSNO ­ , the sulfane sulfur equivalents are released in the form of inorganic polysulfides (HSx ­ ). HSx ­ were shown to be important mediators in H 2 S biology by inducing protein Cys persulfidation. However, HSx ­ are readily reduced by the glutathione and thioredoxin systems inside the cell. Importantly, we found that SSNO ­ can escape these reducing machineries and hence we hypothesize that it could serve as a sulfane sulfur carrier for sustained and long range HSx ­ bioavailability. SSNO ­ indeed induced delayed polysulfidation on Cys, GSH, HSA and a slow flux of sulfane sulfur production in HEK 293 cells. Furthermore, HSx ­ were shown to activate TRPA1 channels and our experiments revealed that SSNO ­ can also function as a TRPA1 activator, but with a lasting effect. These observations give credence to our hypothesis that SSNO ­ may be responsible for sustained protein Cys‒polysulfidation and potentially involved in sulfane sulfur trafficking between subcellular compartments.